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Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials
Yang, Man He, Qiangsheng Gao, Fang Nirantharakumar, Krish Qin, Xiwen Page, Amy T Wong, Martin C S Huang, Junjie Kuo, Zi Chong
Yang, Man
He, Qiangsheng
Gao, Fang
Nirantharakumar, Krish
Qin, Xiwen
Page, Amy T
Wong, Martin C S
Huang, Junjie
Kuo, Zi Chong
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2021-12-03
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Abstract
Background: Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods: This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results: We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions: Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs.
Citation
Yang, M., He, Q., Gao, F. et al. Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials. BMC Med 19, 316 (2021). https://doi.org/10.1186/s12916-021-02180-5
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34856983 (pubmed)
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Journal article
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en
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© 2021 The Authors. Published by SpringerNature. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s12916-021-02180-5
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1741-7015
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1741-7015
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This work was supported by the Natural Science Foundation of China (grant number 82003408, 82003524, 82103913), the Startup Fund for the 100 Top Talents Program, SYSU (392012), and Guangdong Provincial Key Laboratory of Digestive Cancer Research, No. 2021B1212040006). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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Licence for published version: Creative Commons Attribution 4.0 International